title: Identification of a novel tumor-associated antigen, cadherin 3/P-cadherin, as a possible target for immunotherapy of pancreatic, gastric, and colorectal cancers.
abstract: OBJECTIVE
  To establish cancer immunotherapy, it is important to identify the tumor-associated antigens (TAA) that are strongly expressed in the tumor cells but not in the normal cells. In this study, to establish an effective anticancer immunotherapy, we tried to identify the useful TAA of pancreatic cancer.
  
  
  METHODS
  Based on a previous genome-wide cDNA microarray analysis of pancreatic cancer, we focused on cadherin 3 (CDH3)/P-cadherin as a novel candidate TAA for anticancer immunotherapy. To identify the HLA-A2 (A*0201)-restricted CTL epitopes of CDH3, we used HLA-A2.1 (HHD) transgenic mice (Tgm). Furthermore, we examined the cytotoxicity against the tumor cells in vitro and in vivo of CTLs specific to CDH3 induced from HLA-A2-positive healthy donors and cancer patients.
  
  
  RESULTS
  CDH3 was overexpressed in the majority of pancreatic cancer and various other malignancies, including gastric and colorectal cancers, but not in their noncancerous counterparts or in many normal adult tissues. In the experiment using HLA-A2.1 Tgm, we found that the CDH3-4(655-663) (FILPVLGAV) and CDH3-7(757-765) (FIIENLKAA) peptides could induce HLA-A2-restricted CTLs in Tgm. In addition, peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A2-positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both CDH3 and HLA-A2. Furthermore, the adoptive transfer of the CDH3-specific CTLs could inhibit the tumor growth of human cancer cells engrafted into nonobese diabetic/severe combined immunodeficiency mice.
  
  
  CONCLUSIONS
  These results suggest that CDH3 is a novel TAA useful for immunotherapy against a broad spectrum of cancers, including pancreatic cancer.
authors.affiliation: Department of Immunogenetics and Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Imai
authors.forename: Shinya
authors.initials: S
authors.lastname: Hirata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Irie
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ikuta
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yokomine
authors.forename: Michiko
authors.initials: M
authors.lastname: Harao
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Nakatsuru
authors.forename: Hidewaki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D019264:Adoptive Transfer; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D000939:Epitopes / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D015789:HLA-A2 Antigen / Q000502:physiology; D006801:Humans; D007167:Immunotherapy; D016086:Lentivirus; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: C512197:CDH3 protein, human; D015820:Cadherins; D000939:Epitopes; D015789:HLA-A2 Antigen; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger